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Biomedical subjects

P Hertz

Publications and source records attributed to P Hertz.

12 recordsLinked to original sources
PubMed1992

The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa.

The endocrine abnormalities along the growth hormone (GH) axis in anorexia nervosa (AN) and in obesity include hypothalamic, pituitary, and peripheral elements. The present study was undertaken to evaluate the effects of these nutritional extremes on GH-binding protein (BP) levels and on Insulin-like growth factor-I (IGF-I) receptors on red blood cells (RBC). Nine patients with AN and 20 obese subjects were compared with normal control children, adolescents, and adults. GH-BP was measured by a binding assay with dextran-coated charcoal separation. IGF-I binding was measured on enriched RBC. Serum GH-BP levels were markedly reduced in the AN patients, and highly increased in the obese. Scatchard analyses showed linear plots with unaltered binding affinities (Ka). The binding capacity (Bmax) was significantly lower than normal control in the AN patients and higher in the obese. GH-BP levels correlated positively with the body mass index (BMI). RBC [125I]IGF-I binding was significantly elevated in the AN patients and low in the obese. Scatchard analyses showed curvilinear plots. The high-affinity constants (Ka1) were slightly, but significantly, higher in the AN patients and in the obese compared with control. The binding capacity of the first binder (Bmax1) was lower in obesity than in AN or control. The low-affinity constants (Ka2) were similar in the three groups, and its binding capacity (Bmax2) was similar in the AN patients and the controls, but significantly lower in the obese. [125I]IGF-I binding correlated negatively and significantly with the BMI and with the GH-BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Growth hormone and insulin-like growth factor-I increase macrophage uptake and degradation of low density lipoprotein.

Hyperlipidemia has been reported in adults with hypopituitarism, and human (h) GH therapy has been shown to lower plasma cholesterol in patients with hypercholesterolemia. Macrophage cholesterol accumulation is an early event in atherosclerosis, and these cells have been shown to respond to GH and insulin-like growth factor (IGF-I). The present study was aimed at investigating the activity of GH and IGF-I in macrophages, and used murine macrophages as a model system to investigate the effects of GH and IGF-I on cellular uptake and metabolism of low density lipoprotein (LDL). The J-774 murine macrophage cell line was shown to bind hGH, to respond to hGH by an increase in cell IGF-I content, and to have specific high affinity binding sites for IGF-I. Mouse peritoneal macrophages and the J-774 macrophage cell line respond to hGH with a dose-dependent stimulation of cellular association and degradation of LDL as well as an enhanced cholesterol esterification rate. A similar response was observed after in vitro treatment of the cells with IGF-I. Preliminary results in human monocyte-derived macrophages showed similar results. The dependency of the effect of hGH on locally produced IGF-I was shown by abrogation of the hGH effect after adding anti-IGF-I antibody to the culture medium. It is concluded that murine macrophages possess the machinery to bind GH, produce IGF-I, and bind IGF-I. This machinery is used by macrophages, and apparently by other cells, to execute GH-dependent IGF-I-mediated stimulation of cellular uptake and metabolism of LDL. This may provide the explanation for both the elevated plasma LDL concentration in patients with GH deficiency and the effect of GH therapy to reduce plasma LDL levels.

Animals↗
PubMed1991

Effects of hypo or hyper-thyroidism on growth hormone-binding protein.

OBJECTIVE: Growth hormone (GH) receptors are influenced by the thyroidal state of experimental animals. It has been suggested that GH-binding protein (BP) might serve as an indirect measure of the GH receptors. The present study was undertaken to investigate the growth hormone binding protein in patients with hypo or hyperthyroidism. PATIENTS: Patients included 42 adults with untreated hyperthyroidism (FT4 greater than 25 pmol/l; TSH less than 0.15 mU/l) and 29 adults and three children with untreated hypothyroidism (FT4 less than 10 pmol/l; TSH greater than 15 mU/l). MEASUREMENTS: Growth hormone binding protein was measured by a binding assay with dextran-coated charcoal separation. The specific binding of 125I-human GH (1 ng) obtained with 50 microliters serum was expressed as a percentage of the total c.p.m. RESULTS: Growth hormone binding protein specific binding in hypothyroid adults and children was significantly lower than in their respective controls in both adults and children (P less than 0.001). In patients with FT4 levels greater than 40 pmol/l, the mean (+/- SEM) growth hormone specific binding (12.89 +/- 0.59%) was higher than in controls (P less than 0.05). However, in 15 hyperthyroid patients with levels of FT4 of 25-40 pmol/l, the mean growth hormone binding protein specific binding (11.22 +/- 0.76%) was not different from that in normal human subjects. The affinity constants (Ka) obtained by Scatchard analysis for the hypothyroid and hyperthyroid patients' sera were not significantly different from that for normal human sera. Binding capacity for the hypothyroid sera was significantly lower (P less than 0.02), while that of hyperthyroid sera was increased (P less than 0.001). CONCLUSIONS: Growth hormone binding protein correlates positively with the thyroid status. It can be indirectly deduced that this reflects a similar relationship with the human GH receptor.

Adult↗
PubMed1991

Decreased serum growth hormone-binding protein in patients with liver cirrhosis.

The recently characterized GH-binding protein (GH-BP) has an amino acid sequence identical to the extracellular domain of the GH receptor. Serum GH-BP reflects the amount of GH receptors, and the liver seems to be their main source. To evaluate the effect of liver disease on GH-BP, 52 patients with liver cirrhosis were studied. Serum GH-BP was measured by a binding assay with dextran-coated charcoal separation. Levels of GH-BP were correlated against the clinical state, assessed by Pugh's score. The GH-BP of 31 Pugh's class A patients was 9.7 +/- 0.5%/50 microL serum, and that of 21 Pugh's class B and C patients was 7.2 +/- 0.5%/50 microL serum compared to 11.3 +/- 0.5%/50 microL serum in age-matched controls. GH-BP correlated negatively with Pugh's score and serum bilirubin, and positively with serum albumin. It did not correlate with serum liver enzymes or serum insulin-like growth factor-I. Scatchard analysis of GH binding to the GH-BP revealed similar binding affinities in Pugh's A, B, and C patients and controls. The binding capacity in cirrhosis was significantly lower than that in controls. We conclude that serum GH-BP is controlled mainly by the liver and can provide an additional measure of disease severity in liver cirrhosis.

Adult↗
PubMed1990

Identification of growth hormone binding protein in rat serum.

The present report describes the initial characterization of a specific, high-affinity growth hormone binding protein (GH-BP) in adult male rat serum. GH-BP activity was measured by incubation of rat serum with [125I]hGH and [125I]rGH and separation of bound from free GH by dextran-coated charcoal. [125I]hGH binding to rat serum was dependent on serum concentration and incubation time, equilibrium being reached within 10 min both at 4 and 37 degrees C. Binding was rapidly and completely reversible and specific for somatogenic (but not lactogenic) hormones. Scatchard analysis yielded a linear plot with an affinity (Ka) of 1.51 +/- 0.63 x 10(8) M-1. Preliminary data obtained in various physiological conditions showed that GH-BP activity in adult male rats was 5.95 +/- 0.20%/0.1 ml serum. Significantly higher values were obtained in sera of female (21.66 + 0.79%/0.1 ml serum) and pregnant rats (23.02 +/- 1.15%/0.1 ml serum). A closer analysis of these binding values by Scatchard analysis revealed that the binding capacity in pregnant rats (50.5 +/- 5.8 pmol/0.1 ml serum) was significantly higher than in adult female estrous rats (19.2 +/- 6.5 pmol/0.1 ml serum), both being much higher than in adult male rats (2.5 +/- 0.6 pmol/0.1 ml serum). The GH-BP activity of 10-day-old rats was only approximately 63% of the adult male rat value. The presence of high-affinity GH-specific binding protein in rat serum suggests a probable action in regulation of GH activity. The detailed physiological role of rat serum GH-BP is currently being investigated.

Animals↗
PubMed1990

The interrelationship of growth hormone (GH), liver membrane GH receptor, serum GH-binding protein activity, and insulin-like growth factor I in the male rat.

Indirect evidence suggests that the serum GH-binding protein (GH-BP) is related and possibly derived from the GH-receptor. GH, through its specific receptor, is the major regulator of insulin-like growth factor I (IGF-I) synthesis. The present study was undertaken to correlate serum GH-BP activity with liver plasma membrane GH receptors and their effects on serum IGF-I concentration during spontaneous pulsation of rat (r)GH in the normal male rat and after continuous delivery of human (h)GH to hypophysectomized male rats. In the first set of experiments, 45-day-old male rats were decapitated at 15 min intervals for 4 h. Serum GH-BP levels fluctuated with a 60 min lag behind the rGH levels. IGF-I pulsated over a 3-fold concentration range. IGF-I peak levels coincided with one of the rGH peaks, but its periodicity was longer than 3 h. Taken together with our previous studies on the turnover of the GH receptors, we suggest that each GH surge results in individual pulse-related turnover wave of receptor internalization and recycling. This is accompanied by a parallel increase in serum GH-BP activity. The GH and the receptor wave are responsible for an individual secretion pulse of IGF-I. In the second set of experiments male rats were hypophysectomized at 35 days of age. Four days later osmotic minipumps were implanted for continuous delivery of hGH. After 6 days of hGH treatment the rats were killed, blood was collected for hGH, GH-BP, and IGF-I determination, and the livers were removed. Plasma membranes were prepared, and lactogenic and somatogenic binding of [125I]hGH was evaluated. Removal of endogenous ligand was performed by exposing the membranes to 3 M MgCl2. Continuous administration of hGH induced a dose-dependent increase in liver membrane lactogenic and somatogenic binding. Parallel to that increase, serum GH-BP also increased in a dose-dependent manner, and the correlation between serum GH-BP and the liver membrane receptor was significant. Furthermore, hGH induced a dose-dependent increase in IGF-I concentration. There was a close correlation between IGF-I concentration and liver somatogenic receptors. It is concluded that up-regulation of the liver membrane GH receptors is accompanied by increased GH-BP and IGF-I. In both the pulsation experiment and the continuous infusion experiment, GH-BP closely correlated with the liver membrane GH receptor.

Animals↗
PubMed1989

Effects of sex steroids on the response of cultured rat pituitary cells to growth hormone-releasing hormone and somatostatin.

In the male rat, GH secretion is characterized by high amplitude pulses that appear at regular intervals of 3-4 h, with low basal levels between such pulses. In the female, the pulses are irregular and more frequent, with lower amplitudes, while basal secretion is higher. The present study was designed to exclude the indirect effects of sex steroids on the pituitary, enabling investigation of the direct effects of sex steroids on the pituitary. Rats were gonadectomized at 22 days of age, and 12 days later their anterior pituitaries were trypsinized for cell dispersion. Testosterone (T) or 17 beta-estradiol (E2), 5 nM, was added to the medium for 6 days, and subsequently, GRF or somatostatin was added for 4 h. In a perifusion system, the male-derived cell response to GRF was augmented after pretreatment with T, but not with E2. The female-derived cell response to GRF was augmented by E2, but not by T. T increased the sensitivity of the cells to GRF from 3.0-0.03 nM and increased the maximal potency of GH secretion 3-fold. E2 had no significant effect on the sensitivity, but lowered the potency. Somatostatin (1 nM) inhibited GH secretion by 44% in T-treated cells. In E2-treated cells, somatostatin was ineffective. GRF increased the total amount of GH (medium plus cells) in both T- and E2-treated cells, but not in control pituitary cells. It is suggested that T has direct effects on the male somatotroph. By increasing the pituitary cell responses to GRF and somatostatin, T contributes to the high amplitude peak/low baseline pattern of the male. By decreasing the pituitary cell responses to GRF and somatostatin, E2 contributes to the low amplitude peak/high baseline pattern of the female.

Animals↗
PubMed1977

Appointment-keeping behavior re-evaluated.

Many of the traditional approaches to the problem of appointment-keeping behavior have ignored the organizational factors that may be implicated in differentially high broken appointment rates leading to an implicit assumption that low-income and ethnic minority patients will be more likely to break appointments. A case study at a Model Cities Health Center which maintains a kept appointment rate of 85 per cent examined the relationship of broken appointments to age, sex, ethnic background, and payment mechanisms. The results suggest alternative explanations for differentially high broken appointments centering on the role of the institution in reinforcing appointment-keeping behavior.

Adult↗
PubMed1976

Hypercalcemia of acute renal failure. Clinical significance and pathogenesis.

Hypocalcemia is a frequent accompaniment of acute renal failure, but paradoxically hypercalcemia also has been described in association with acute renal failure. In this paper we describe two patients who provide some insights into both the potential clinical importance and mechanism of the hypercalcemia associated with acute renal failure. The clinical significance is emphasized by the presence of diffuse metastatic calcification observed at postmortem examination in one patient. In both patients the increase in serum calcium concentration was not coincident with a decrease in serum phosphorus concentration; when measured in one patient, serum levels of parathyroid hormone were undetectable. These findings, along with the consistent association with rhabdomyolosis, support the proposal that the hypercalcemia of acute renal failure is caused by dissolution of dystrophic calcifications in traumatized muscle and may lead to severe metastatic calcifications.

Acute Kidney Injury↗